The goal of this project is to develop framework linkage maps of two acrocentric human chromosomes: 13 and 15. The maps will consist of index markers with a heterozygosity of 0.7 or greater that detect loci that are no more than 10 to 15 cM apart. Within the first two years, 40 random highly polymorphic markers will be identified for each chromosome. This number is sufficient for a 95% probability that loci are no further than 10 cM apart. Highly polymorphic markers will be a) variable lengths of "CA" dinucleotide repeat sequences and other di-, tri-, and tetra-nucleotide repeat sequences typed with the polymerase chain reaction (PCR) b) Variable Alu polymorphisms (AluVpa) detected with PCR c) VNTR polymorphisms detected by Southern blotting d) polymorphisms in the 3' regions of genes known to reside on chromosomes 13 and 15. Once the heterozygosity of a particular polymorphic system has been determined to be approximately 0.7 in a set of 100 unrelated Caucasian individuals, the CEPH families will be typed for the polymorphism. Highly informative markers on these chromosomes that have been identified by other workers will also be typed if this has not already been performed. In order to construct the framework maps, two- point and multipoint linkage analysis will be performed with the program LINKAGE. The presence of undetected typing errors will be allowed for in the analysis. In the third year a targeted approach will be used to fill in gaps: a) by identifying cosmid, large insert bacteriophage or YAC clones with probes detecting loci with low heterozygosity that have been previously mapped to such intervals b) by screening for human clones from radiation hybrids containing DNA segments from these intervals c) by fluorescence in situ hybridization to identify cosmids flanked by other clones known to detect loci that are more than 10 - 15 cM apart. These recombinants will be used to develop highly informative markers. Markers for loci closer than 10 cM will be used to move towards a 5 cM map. All markers and data will be freely available, and will be deposited in repositories deemed appropriate by the NCHGR.